Related Experiment Video
Updated: Jun 23, 2025
Preclinical Assessment of the Bioactivity of the Anticancer Coumarin OT48 by Spheroids, Colony Formation Assays, and Zebrafish Xenografts
Published on: June 26, 2018
Targeting Oral Cancer: In Silico Docking Studies of Phytochemicals on Oncogenic Molecular Markers
Priyadarshini G1, Gheena Sukumaran1, Dilipan E1
1Department of Oral and Maxillofacial Pathology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences,Saveetha University, Chennai, India.
Objective:
Molecular docking is a key tool in structural molecular biology and computer-assisted drug design. Oral carcinogenesis is a complex, multistep process in which genetic events within signal transduction pathways governing normal cellular physiology are quantitatively or qualitatively altered. There are various molecular targets like Cyclin D and PI3k- alpha Ras Binding Domain receptor protein involved in the pathogenesis of Oral Squamous Cell Carcinoma. The aim of the study is to demonstrate the computer aided drug design to identify a potent natural molecule for targeting cyclin D4 and PI3K RAS binding protein.
Materials And Methods:
Target selection (Cyclin D1 and PI3K-alpha Ras Binding Domain receptor) was done and structures were derived from protein data bank. Ligands (Apigenin, Chrysoeriol and Luteolin) selection was done and structure derived. Final docking was performed by Autodock.
Results:
From the docking results it can be seen that luteolin has the highest binding energy (-5.45) with the Cyclin D receptor molecule followed by Chrysoeriol (-4.99) and Apigenin (-4.96). The binding energies of the ligands against PI3K-alpha Ras Binding Domain receptors were Apigenin (-4.51), Chrysoeriol (-4.6) and Luteolin (-4.56).
Conclusion:
The study concludes that all the three selected ligands possess high binding energy with both the target proteins involved in carcinogenesis with highest binding energy possessed by Luteolin against the Cyclin D receptor and by Chrysoeriol against PI3K-RAS binding protein. Thus their activity can be utilized to derive potential Anti-cancer therapeutic drugs.
Insights
Natural compounds luteolin and chrysoeriol show potent binding to key oral cancer targets, Cyclin D and PI3K-RAS. This computer-aided drug design study identifies promising candidates for developing novel anti-cancer therapeutics.
Area of Science:
- Computational biology
- Structural molecular biology
- Drug discovery
Background:
- Oral carcinogenesis involves complex genetic alterations in signal transduction pathways.
- Cyclin D and PI3K-alpha Ras Binding Domain receptor proteins are key targets in Oral Squamous Cell Carcinoma pathogenesis.
Purpose of the Study:
- To utilize computer-aided drug design to identify natural molecules targeting Cyclin D4 and PI3K RAS binding protein.
- To evaluate the binding potential of selected natural compounds against crucial oral cancer targets.
Main Methods:
- Selected Cyclin D1 and PI3K-alpha Ras Binding Domain receptor structures from the Protein Data Bank.
- Chosen natural ligands: Apigenin, Chrysoeriol, and Luteolin.
- Performed molecular docking simulations using Autodock.
Main Results:
- Luteolin exhibited the highest binding energy (-5.45 kcal/mol) with the Cyclin D receptor.
- Chrysoeriol showed the highest binding energy (-4.6 kcal/mol) with the PI3K-alpha Ras Binding Domain receptor.
- All three ligands demonstrated significant binding affinities to both target proteins.
Conclusions:
- Luteolin and Chrysoeriol are potent inhibitors of Cyclin D and PI3K-RAS, respectively.
- The natural compounds show potential for developing novel anti-cancer drugs.
- Computer-aided drug design effectively identified promising therapeutic candidates.
